Macbecin I and herbimycin A are recently isolated ansamycin antibiotics which elicit a broad spectrum of biological response including antitumor, antiviral, antifungal and herbicidal activity. The principal objective of this investigation is the development of a convergent, stereocontrolled synthesis of macbecin I and related antitumor ansamycins. A key feature of the proposed synthetic plan is the rapid development of the macbecin I and herbimycin A ansa systems using a series of highly stereoselective sigmatropic homologations. Preliminary studies have resulted in an efficient, preparative-scale route to the fully-functionalized ansa system of macbecin I. The convergent nature of the proposed synthetic plan and the intrinsic versatility of the iterative sigmatropic strategy for elaboration of the ansa systems of macbecin I and related compounds make the proposed scheme well suited for the synthesis of individual site-modified analogs of the parents compounds. The proposed synthetic studies will generate advanced intermediate which incorporate specific structural elements of the antitumor ansamycins. The intermediates will be screened for antitumor, antifungal and antiviral activity. The long-term objective of our synthetic program is the development of a comprehensive strategy for the construction of highly-oxygenated acyclic targets which is amenable to the preparative scale synthesis of complex acyclic and macrocyclic compounds. Towards this end, we will examine new classes of [2,3] Wittig substrates which have direct relevance to the preparation of biologically active, polyketide-derived natural products. We will additionally investigate the application of the serial sigmatropic strategy to the synthesis of the ansa systems of the antitumor/antiviral agents streptovaricins C and D. Specific strategies for selective functionalization of advanced intermediates resulting from serial sigmatropic homologation will be examined, with the goal of developing effective new methodology for the preparation of these structurally related synthetic targets.